Pyrimethamine
Synonyms :
Pyrimethamine / Sulfadoxine, Pyrimethamine / Sulphadoxine, Sulfadoxine + Pyrimethamine
Mechanism :
Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. However, the 4-amino-quinoline compounds are more effective against the erythrocytic schizonts. It does not destroy gametocytes, but arrests sporogony in the mosquito.
Indication :
- Toxoplasma
- Malaria treatment (Given along with sulfadoxine)
Contraindications :
Contraindicated in patients with known hypersensitivity to pyrimethamine or to any component of the formulation. Use of the drug is also contraindicated in patients with documented megaloblastic anemia due to folate deficiency.
Dosing :
Toxoplasmosis in infants:
Pyrimethamine along with
sulfadiazine (50 mg/kg 2 times daily) and calcium folinate (folinic acid) (15 mg/kg three times in a week) are given for 12 months. Pyrimethamine is started with loading dose of 1 mg/kg/dose 2 times daily for 2 days, then 1 mg/kg/dose once daily for 6 months followed by 1 mg/kg/dose thrice in a week for 6 months. Prednisolone at 0.5 mg/kg/dose 2 times daily is also given until signs of CNS inflammation or active chorioretinitis have settled and then tapered.
Ocular toxoplasmosis, reactivation of toxoplasmosis during HIV Infection and toxoplasmosis in immune-compromised child with protracted or incapacitating illness:
2 mg/kg loading dose for 2 days followed by 1 mg/kg in <12 years and 25-100 mg in 12-18 years olds for 8 weeks to prevent relapse in HIV patients followed by maintenance of a quarter to half of the starting dose indefinitely.
Malaria treatment:
The fixed dose combination (FDC) contains 20 parts Sulfadoxine and 1 part pyrimethamine. Available as 500/25 mg tablet of sulfadoxine/pyrimethamine)
1 mg/kg PO of pyrimethamine single dose.
Adverse Effect :
Hypersensitivity reactions, occasionally severe (such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and anaphylaxis), and hyperphenylalaninemia, can occur particularly when pyrimethamine is administered concomitantly with a sulfonamide. With doses of pyrimethamine used for the treatment of toxoplasmosis, anorexia and vomiting may occur. Doses used in toxoplasmosis may produce megaloblastic anemia, leukopenia, thrombocytopenia, pancytopenia, atrophic glossitis, hematuria, and disorders of cardiac rhythm.
Interaction :
Antifolic drugs or agents: Associated with myelosuppression including sulfonamides or trimethoprim-sulfamethoxazole combinations, proguanil, zidovudine, or cytostatic agents (e.g., methotrexate) while the patient is receiving pyrimethamine, may increase the risk of bone marrow suppression. Folinic acid (leucovorin) should be administered until normal hematopoiesis is restored. Mild hepatotoxicity has been reported in some patients when lorazepam and pyrimethamine were administered concomitantly.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in normal renal function |
| HD | Not dialysed. Dose as in normal renal function |
| HDF/High flux | Unknown dialysability. Dose as in normal renal function |
| CAV/VVHD | Not dialysed. Dose as in normal renal function |
Hepatic Dose :
Dose adjustment may be required as pyrimethamine undergoes hepatic metabolism. In hepatic impairment therapy, start with low dose and monitor.